Fields such as biochemistry, geochemistry, nutrition, organic chemistry, physiology, and pharmacology, use elemental analysis in a variety of applications. (See Griffin, I. J., J. Anal. At. Spectrom. 2002, 17, 1186-1193.) Elemental mass spectrometry offers a sensitive and relatively simple approach for quantitative analysis. Elemental mass spectrometry works by breaking the molecules into their constituent atoms, and then providing a constant response factor for each element, regardless of the chemical structure of compounds. Therefore, quantitative concentration measurements, as well as isotope ratio analysis, can be performed in the absence of individual standards for compounds of interest. Further, using elemental mass spectrometry, isotopic labeling patterns may be exploited to identify a geographic origin of a sample, to study a drug's metabolism (See Branch et al., J. Anal. At. Spectrom. 2003, 18, 17-22), or to monitor levels of biological compounds. (See Jorabchi et al., Anal. Chem. 2005, 77, 5402-5406.)
Chemical Reaction Interface Mass Spectrometry (CRIMS) is an example of a technique used in elemental mass spectrometry. CRIMS provides an analytical method for the selective detection of elements or isotopes from chemical and biological analytes. In particular, quantitative and isotopic analysis of compounds with high molecular weight, for example biological proteins, is hindered by the complexity of spectra and mass limits of mass spectrometry. CRIMS works by breaking molecules, especially large molecules into elemental constituents, which can readily be detected by a mass spectrometer. By breaking apart larger molecules, CRIMS provides a simple method to monitor the elemental content, and thereby the concentration of molecules and isotopic signature of elements. The ability of CRIMS to analyze large molecular analytes has advantages in fields that require the analysis of large non-volatile chemicals.
In conventional CRIMS, an analyte is introduced into a low pressure and high temperature plasma gas, referred to as the chemical reaction interface (CRI). Within the plasma, an analyte reacts with a reactant gas, breaking the chemical structure of the analyte into small and stable element specific reaction products. For illustration, elements present in an analyte, such as carbon, nitrogen, and bromine are liberated as CO2, NO2, and HBr (when hydrogen atoms are present). Sulfur may be converted to SO3, SO4, and HSO4 (when hydrogen atoms are present) upon reaction of analyte with oxygen.
The elemental reaction products from the plasma stream are then ionized, which allows their identification and quantification by mass spectrometry. Traditionally, ionization is performed via electron impact after the products are transferred to a high vacuum region in the mass spectrometer. Methods such as electron impact generally limit efficient ionization to positive ion formation, limiting the utility of CRIMS in detecting negative ions. Further, the high-vacuum requirement of electron impact limits the analyte throughput into the ion source. This leads to loss of sensitivity in CRIMS as majority of the analyte stream coming out of the reaction interface is pumped away to reduce the pressure.
Elements such as fluorine cannot be readily quantified by detecting positively charged ions due to high ionization potential. Yet current estimates state that 20% of drugs and 30% of agrochemicals contain fluorine. Current techniques for halogen-specific detection in gas chromatography (GC) and liquid chromatography (LC) primarily focus on the use of plasma emission spectroscopy and plasma mass spectrometry as detectors. These techniques rely on positive ion generation or excitation of halogens. But considering the high ionization potential of certain elements, e.g., halogens, these techniques are not efficient.
There is demand in the field for elemental mass spectrometric analysis that can efficiently generate ions without a loss of sensitivity by, for example, allowing for the detection of negatively charged ions and/or facilitating ionization at higher pressures.